Polyphenolic compounds (including flavonoids, chalcones, phenolic acids, and furanocoumarins) represent a common part of our diet, but are also the active ingredients of several dietary supplements and/or medications. These compounds undergo extensive metabolism by human biotransformation enzymes and the microbial flora of the colon. CYP2D6 enzyme metabolizes approximately 25% of the drugs, some of which has narrow therapeutic window. Therefore, its inhibition can lead to the development of pharmacokinetic interactions and the disruption of drug therapy. In this study, the inhibitory effects of 17 plant-derived compounds and 19 colonic flavonoid metabolites on CYP2D6 were examined, employing two assays with different test substrates. The O-demethylation of dextromethorphan was tested employing CypExpress 2D6 kit coupled to HPLC analysis; while the O-demethylation of another CYP2D6 specific substrate (AMMC) was investigated in a plate reader assay with BioVision Fluorometric CYP2D6 kit. Interestingly, some compounds (e.g., bergamottin) inhibited both dextromethorphan and AMMC demethylation; however, certain substances proved to be inhibitors only in one of the assays applied. Our results demonstrate that some polyphenols and colonic metabolites are inhibitors of CYP2D6-catalyzed reactions. Nevertheless, the inhibitory effects showed strong substrate dependence.
- MeSH
- acetamidy metabolismus MeSH
- cytochrom P-450 CYP2D6 metabolismus MeSH
- dextromethorfan metabolismus MeSH
- flavonoidy farmakologie MeSH
- inhibitory cytochromu P450 CYP2D6 farmakologie MeSH
- kolon metabolismus MeSH
- lidé MeSH
- polyfenoly metabolismus farmakologie MeSH
- pyridaziny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- cytochrom P-450 CYP2D6 * genetika účinky léků MeSH
- dospělí MeSH
- genotyp MeSH
- inhibitory cytochromu P450 CYP2D6 aplikace a dávkování farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru epidemiologie genetika MeSH
- nádorové biomarkery genetika MeSH
- nádory prsu farmakoterapie genetika MeSH
- tamoxifen farmakologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
